Long-Term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study

• Published in: The journal of clinical endocrinology and metabolism 2020-10, Vol.105 (10), p.e3638-e3649
• Main Authors: Scott, Emma S, Januszewski, Andrzej S, O’Connell, Rachel, Fulcher, Gregory, Scott, Russell, Kesaniemi, Antero, Wu, Linda, Colagiuri, Stephen, Keech, Anthony, Jenkins, Alicia J
• Format: Article
• Language: English
• Subjects: Aged; Australia - epidemiology; Biological Variation, Individual; Blood Glucose - analysis; Blood sugar; Cardiovascular diseases; Complications and side effects; Development and progression; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetic angiopathies; Diabetic Angiopathies - epidemiology; Fasting; Fasting - blood; Female; Finland - epidemiology; Glucose; Glycated Hemoglobin A - analysis; Health aspects; Hemoglobin; Humans; Laboratory testing; Male; Microvasculature; Middle Aged; Mortality; New Zealand - epidemiology; Prospective Studies; Risk factors; Type 2 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa361

Abstract Aims To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. Methods In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. Results Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P < 0.01; and HR 1.01 [95% CI, 1.00-1.01] P < 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04]; and HR 1.01 [95% CI, 1.00-1.02], both P < 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P < 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P < 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06]; and HR 1.01 [95% CI, 1.01-1.02], both P < 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07]; and HR 1.02 [95% CI, 1.01-1.03], both P < 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P < 0.05). Conclusions Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.